ARHGEF26 is a Rho guanine nucleotide exchange factor that activates RhoG GTPase by catalyzing GDP-to-GTP exchange, functioning as a critical regulator of cytoskeletal dynamics and cell migration 1. Mechanistically, ARHGEF26 promotes membrane ruffles during macropinocytosis and regulates adherens junction stability through complex formation with Scribble and Dlg1 polarity proteins 2. In endothelial cells, ARHGEF26 enhances angiogenesis by promoting VEGFR2 macropinocytosis and VEGF-dependent signaling, with CAD-risk variants conferring gain-of-function effects 3. Pathologically, ARHGEF26 plays multifaceted roles across diverse diseases: it facilitates Salmonella invasion and infection-induced inflammation through SopB/SopE-dependent mechanisms 1, mediates glucocorticoid-induced trabecular meshwork cell myofibroblast transdifferentiation in glaucoma development 4, and serves as a downregulated biomarker in diabetic kidney disease podocytes 5. Additionally, ARHGEF26 is phosphorylated downstream of PKCζ in calcium-sensing receptor-driven breast cancer cell migration 6, and its expression is suppressed by miR-27a-3p to limit vascular smooth muscle cell proliferation during neointima formation 7. These findings establish ARHGEF26 as a pleiotropic regulator with therapeutic potential across infectious disease, vascular, metabolic, and oncologic contexts.